This invention relates to instruments and methods for performing non-invasive measurements of analyte concentrations and for monitoring, analyzing and regulating tissue status, such as tissue glucose levels.
Diabetes is a chronic life threatening disease for which there is presently no cure. It is the fourth leading cause of death by disease in the U.S. and at least 90 million people worldwide are estimated to be diabetic. Diabetes is a disease in which the body does not properly produce or respond to insulin. The high glucose levels that can result from this affliction can cause severe damage to vital organs, such as the heart, eyes and kidneys.
Type I diabetes juvenile diabetes or insulin-dependent diabetes mellitus) is the most severe form of the disease comprising approximately 10% of the diabetes cases in the United States. Type I diabetics must receive daily injections of insulin in order to sustain life. Type II diabetes, (adult onset diabetes or non-insulin dependent diabetes mellitus) comprises the other 90% of the diabetes cases. Type II diabetes is often manageable with dietary modifications and physical exercise, but may still require treatment with insulin or other medications. Because the management of glucose to near normal levels can prevent the onset and the progression of complications of diabetes, persons afflicted with either form of the disease are instructed to monitor their blood glucose level in order to assure that the appropriate level is achieved and maintained.
Traditional methods of monitoring the blood glucose level of an individual require that blood be withdrawn. This method is painful, inconvenient, costly and poses the risk of infection. Another glucose measuring method involves urine analysis, which, aside from being inconvenient, may not reflect the current status of the patient""s blood glucose because glucose appears in the urine only after a significant period of elevated levels of blood glucose. An additional inconvenience of these traditional methods is that they require testing supplies such as collection receptacles, syringes, glucose measuring devices and test kits. Although disposable supplies have been developed, they are costly and can require special methods for disposal.
Many attempts have been made to develop a painless, non-invasive external device to monitor glucose levels. Various approaches have included electrochemical and spectroscopic technologies, such as near-infrared spectroscopy and Raman Spectroscopy. Despite extensive efforts, however, none of these methods appears to have yielded a non-invasive device or method for the in vivo measurement of glucose that is sufficiently accurate, reliable, convenient and cost-effective for routine use.
The invention overcomes problems and disadvantages associated with current strategies and designs and provides new instruments and methods for monitoring, analyzing and regulating in vivo glucose levels or other analyte levels in an individual.
In one general aspect, the invention features a non-invasive glucose monitoring instrument useful in vivo. The instrument may comprise a radiation source capable of directing radiation to a portion of the exterior or interior surface of a patient. That surface may be a mucosal area such as the gums and other mucosal areas, the eyeballs and surrounding areas such as the eyelids and, preferably, the skin. The source emits radiation at a wavelength that excites a target within the patient such that the excited target provides a glucose level indication of the patient. A glucose level indication is a quantitative or relative measurement that correlates with the blood glucose content or concentration of the patient. The instrument may further comprise a radiation detector positioned to receive radiation emitted from the excited target, and a processing circuit operatively connected to the radiation detector that translates emitted radiation to a measurable signal to obtain the glucose level indication. The target is not glucose itself, but a molecular component of the patient such as, for example, a component of skin or other tissue, that reflects or is sensitive to glucose concentration, such as tryptophan or collagen cross-links. Suitable targets are structural components, and compounds and molecules that reflect alterations in the environment of matrix components of the tissue and are sensitive to or correlate with tissue glucose concentration. The target provides an emitted fluorescence signal that is related to the patient""s blood glucose level. The radiation detector is responsive to the emission band of the target or species in the skin. Preferably the radiation is ultraviolet radiation or light. The emitted radiation is preferably fluorescence radiation from the excitation of the non-glucose target. The instrument may further include means for measuring scattering re-emitted from the irradiated skin. The radiation emitted from the excited target and signal therefrom correlates with the blood glucose of the patient.
Another aspect of the invention relates to an instrument for assessing changes in the superficial structural matrix of the skin or other tissue of a patient comprising means for measuring fluorescence, and means for measuring scattering.
Another aspect of the invention relates to an instrument for assessing changes in the environment of matrix components of the skin or other tissue of a patient comprising means for measuring fluorescence, and means for measuring scattering. Preferred embodiments further include means for combining signals from the means for measuring fluorescence and the means for measuring scattering.
Another aspect of the invention relates to a non-invasive method of detecting or assessing a glucose level comprising exciting a target that, in an excited state, is indicative of the glucose level of a patient, detecting the amount of radiation emitted by the target, and determining the glucose level of the patient from the amount of radiation detected. The target is preferably a molecular species in the skin. Preferred targets are tryptophan or a matrix target, like PDCCL, which are excited by ultraviolet radiation and act as bioamplifiers or bioreporters. Targets may be structural matrix or cellular components. Suitable targets reflect alterations within the environment of matrix components of the skin or other tissue and act as bioamplifiers or bioreporters when excited with ultraviolet radiation.
Still another aspect of the invention relates to a non-invasive method of assessing a change in the superficial structural matrix of a tissue, or a change in the environment of matrix components, comprising exposing the tissue to radiation at a first wavelength, detecting an amount of fluorescence emitted by exposed tissue, exposing the tissue to radiation of a second wavelength, detecting an amount of scattering re-emitted from the exposed tissue, and deriving an indication representative of the change in the superficial structural matrix of the tissue, or a change in tissue matrix components or their environment, based on of the amount of fluorescence detected and the amount of scattering detected.
Other objects and advantages of the invention are set forth in part in the description which follows, and in part, will be obvious from this description, or may be learned from the practice of the invention.